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胸苷酸合成酶的表达水平是预测结直肠癌对5-氟尿嘧啶化疗敏感性的良好指标。

Expression level of thymidylate synthase is a good predictor of chemosensitivity to 5-fluorouracil in colorectal cancer.

作者信息

Inoue Tamotsu, Hibi Kenji, Nakayama Goro, Komatsu Yoshinao, Fukuoka Tomoki, Kodera Yasuhiro, Ito Katsuki, Akiyama Seiji, Nakao Akimasa

机构信息

Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.

出版信息

J Gastroenterol. 2005 Feb;40(2):143-7. doi: 10.1007/s00535-004-1512-9.

DOI:10.1007/s00535-004-1512-9
PMID:15770397
Abstract

BACKGROUND

It is important to seek the appropriate chemotherapy drugs to effectively eliminate colorectal cancers. To avoid unnecessary medication and uncomfortable side effects, it is important to estimate the chemosensitivity of cancers to 5-fluorouracil (5-FU) before chemotherapy.

METHODS

We examined thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene expressions in 23 colorectal cancers, using quantitative reverse transcription-polymerase chain reaction (RT-PCR). We then evaluated the relationship between TS and DPD gene expression levels and the sensitivity of colorectal cancers to 5-FU, as determined by histoculture drug response assay (HDRA).

RESULTS

A significant increase in the TS expression score was observed in 5-FU-sensitive colorectal cancers (0.57 +/- 0.19) compared to 5-FU-resistant ones (1.16 +/- 0.98; P = 0.029), whereas no significant differences in DPD expression scores were observed in 5-FU-sensitive colorectal cancers (0.86 +/- 1.19) compared to 5-FU-resistant ones (0.56 +/- 1.05; P = 0.603).

CONCLUSIONS

TS mRNA may be useful as a predictor of the 5-FU chemosensitivity of colorectal cancers.

摘要

背景

寻找合适的化疗药物以有效消除结直肠癌至关重要。为避免不必要的用药及不适的副作用,在化疗前评估癌症对5-氟尿嘧啶(5-FU)的化疗敏感性很重要。

方法

我们采用定量逆转录-聚合酶链反应(RT-PCR)检测了23例结直肠癌中胸苷酸合成酶(TS)和二氢嘧啶脱氢酶(DPD)基因的表达。然后我们评估了TS和DPD基因表达水平与结直肠癌对5-FU敏感性之间的关系,该敏感性通过组织培养药物反应试验(HDRA)确定。

结果

与5-FU耐药的结直肠癌(1.16±0.98;P = 0.029)相比,5-FU敏感的结直肠癌(0.57±0.19)中观察到TS表达评分显著增加,而与5-FU耐药的结直肠癌(0.56±1.05;P = 0.603)相比,5-FU敏感的结直肠癌(0.86±1.19)中DPD表达评分未观察到显著差异。

结论

TS mRNA可能作为结直肠癌5-FU化疗敏感性的预测指标。

相似文献

1
Expression level of thymidylate synthase is a good predictor of chemosensitivity to 5-fluorouracil in colorectal cancer.胸苷酸合成酶的表达水平是预测结直肠癌对5-氟尿嘧啶化疗敏感性的良好指标。
J Gastroenterol. 2005 Feb;40(2):143-7. doi: 10.1007/s00535-004-1512-9.
2
Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression levels: predictors for survival in colorectal cancer patients receiving adjuvant 5-fluorouracil.胸苷酸合成酶和二氢嘧啶脱氢酶mRNA表达水平:接受辅助性5-氟尿嘧啶治疗的结直肠癌患者生存情况的预测指标
Clin Cancer Res. 2003 Sep 15;9(11):4116-24.
3
Combination of dihydropyrimidine dehydrogenase and thymidylate synthase gene expressions in primary tumors as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer.原发性肿瘤中二氢嘧啶脱氢酶和胸苷酸合成酶基因表达的联合作为转移性结直肠癌氟嘧啶类化疗疗效的预测参数。
Clin Cancer Res. 2003 Feb;9(2):786-91.
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Predictive role of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase expression in colorectal cancer patients receiving adjuvant 5-fluorouracil.胸苷酸合成酶、二氢嘧啶脱氢酶和胸苷磷酸化酶表达在接受辅助性5-氟尿嘧啶治疗的结直肠癌患者中的预测作用
Oncology. 2006;70(5):366-77. doi: 10.1159/000098110. Epub 2006 Dec 15.
5
Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase, and thymidine phosphorylase.对5-氟尿嘧啶有反应的结直肠肿瘤,其二氢嘧啶脱氢酶、胸苷酸合成酶和胸苷磷酸化酶的基因表达水平较低。
Clin Cancer Res. 2000 Apr;6(4):1322-7.
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Expression level of thymidylate synthase mRNA reflects 5-fluorouracil sensitivity with low dose and long duration in primary colorectal cancer.胸苷酸合成酶mRNA的表达水平反映了原发性结直肠癌在低剂量、长时间使用5-氟尿嘧啶时的敏感性。
Cancer Chemother Pharmacol. 2008 Apr;61(4):587-94. doi: 10.1007/s00280-007-0511-y. Epub 2007 May 23.
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Thymidylate synthase and dihydropyrimidine dehydrogenase gene expression in breast cancer predicts 5-FU sensitivity by a histocultural drug sensitivity test.胸苷酸合成酶和二氢嘧啶脱氢酶基因在乳腺癌中的表达通过组织培养药物敏感性试验预测5-氟尿嘧啶敏感性。
Cancer Lett. 2005 Jun 1;223(1):103-11. doi: 10.1016/j.canlet.2004.09.020.
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Correlation between thymidylate synthase and dihydropyrimidine dehydrogenase mRNA level and in vitro chemosensitivity to 5-fluorouracil, in relation to differentiation in gastric cancer.胸苷酸合成酶与二氢嘧啶脱氢酶mRNA水平之间的相关性以及与胃癌分化相关的对5-氟尿嘧啶的体外化疗敏感性。
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Correlation between chemosensitivity and mRNA expression level of 5-fluorouracil-related metabolic enzymes during liver metastasis of colorectal cancer.结直肠癌肝转移过程中5-氟尿嘧啶相关代谢酶的化学敏感性与mRNA表达水平的相关性
Oncol Rep. 2006 Apr;15(4):875-82.
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[Expression of mRNA levels of thymidylate synthase, dihydropyrimidine dehydrogenase, and orotate phosphoribosyltransferase of colorectal cancer--relationships among mRNA levels in association with response to 5-FU based treatment].[结直肠癌中胸苷酸合成酶、二氢嘧啶脱氢酶和乳清酸磷酸核糖转移酶的mRNA水平表达——基于5-氟尿嘧啶治疗反应的mRNA水平之间的关系]
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